rs587776660

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM4PP3PP5

The NM_000455.5(STK11):​c.908_916del​(p.Ile303_His306delinsAsn) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. I303I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

STK11
NM_000455.5 inframe_deletion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
STK11 (HGNC:11389): (serine/threonine kinase 11) The protein encoded by this gene is a serine/threonine kinase that regulates cell polarity and energy metabolism and functions as a tumor suppressor. Mutations in this gene have been associated with the autosomal dominant Peutz-Jeghers syndrome, as well as with skin, pancreatic, and testicular cancers. [provided by RefSeq, May 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM1
In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 16 uncertain in NM_000455.5
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000455.5.
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
Variant 19-1221993-ATCCGGCAGC-A is Pathogenic according to our data. Variant chr19-1221993-ATCCGGCAGC-A is described in ClinVar as [Pathogenic]. Clinvar id is 7446.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
STK11NM_000455.5 linkuse as main transcriptc.908_916del p.Ile303_His306delinsAsn inframe_deletion 7/10 ENST00000326873.12
STK11NM_001407255.1 linkuse as main transcriptc.908_916del p.Ile303_His306delinsAsn inframe_deletion 7/9
STK11NR_176325.1 linkuse as main transcriptn.2175_2183del non_coding_transcript_exon_variant 8/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
STK11ENST00000326873.12 linkuse as main transcriptc.908_916del p.Ile303_His306delinsAsn inframe_deletion 7/101 NM_000455.5 P1Q15831-1

Frequencies

GnomAD3 genomes
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Peutz-Jeghers syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 08, 1998- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587776660; hg19: chr19-1221992; API